Dr. Brian Flumerfelt
Ph.D. University of Cambridge
Transmitters and receptors are vitally important in nervous activity, and the functional impairment which characterizes many neurological diseases is frequently due to imbalances in their relative concentrations within specific areas of the brain. A greater understanding of their interaction may thus provide new opportunities for therapy through pharmacological intervention at the transmitter-receptor interface. The basal ganglia provide unique opportunities to study synaptic interaction due to their numerous transmitters and receptors, and their unusual structural features at the subnuclear and ultrastructural level. By localizing transmitters, receptors and transporters it is possible to study the ways in which these neurochemicals enable cells to communicate and interact. Techniques based in molecular biology are also being employed to study changes in the levels of these substances in response to various influences. Three research projects which are currently in progress are as follows:
Functional and chemical organization in the neostriatum
The neostriatum of the brain plays an important role in the control of motor activity and muscular coordination. Pathological changes in the structural and chemical integrity of this region underlie such disorders as Parkinson's and Huntington's disease. We are currently conducting a series of experiments designed to provide fundamental information concerning the functional organization of this important structure in health and disease.
Neural transplants in the neostriatum
Transplantation of healthy nervous tissue to diseased areas of the brain promises to provide an important new treatment for a number of degenerative neurological disorders. Our research is designed to provide a better understanding of those factors which underlie functional improvement following grafting and which govern interaction at the graft-host interface. Our ongoing studies involve transplantation of dopaminergic neurons into the dopamine depleted neostriatum of rats. This rat model of Parkinson's disease provides an opportunity to study the potential therapeutic benefits of cell transplantation as a clinical strategy.
Gene expression in the basal ganglia
The techniques of molecular biology represent powerful new tools by which functional organization in the brain may be investigated. Using differential display and in situ hybridization, we have recently obtained and confirmed the regional expression of six MRNA species in the basal ganglia. Two of these genes appear to be completely novel, showing no homology to any known sequences. This data promises to provide important new insights into basal ganglia function.
Hussain, N., Flumerfelt, B.A. and Rajakumar, N. (2003) Glutamatergic regulation of long-term grafts of fetal lateral ganglionic eminence in a rat model of Huntington's disease. Neurobiology of Disease 15: 648-653.
Hussain, N., Flumerfelt, B.A. and Rajakumar, N. (2001) Glutamatergic regulation of Haloperidol-induced c-fos expression in the striatum and nucleus accumbens. Neuroscience 102: 391-399.
Rushlow, W.J., Rajakumar, B., Flumerfelt, B.A. , Naus, C.C.G. and Rajakumar, N. (2000) Changes in CarG-binding protein A expression levels following injection(s) of the D1-dopamine agonist SKF-82958 in the intact and 6-hydroxydopamine-lesioned rat. Neuroscience 98: 69-78.
Rushlow, W.J., Rajakumar, N., Flumerfelt, B.A. and Naus, C.C.G. (1999) Characterization of CArG-BPB initially identified by differential display. Neuroscience 94: 637-649.